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Associations between the Leptin Receptor Gene and Adiposity in Middle-Aged Caucasian Males from the HERITAGE Family Study¹

Physical Activity Sciences Laboratory (Y.C.C., J.G., L.P.), Laval University, Ste-Foy, Québec, Canada, G1K 7P4; Department of Health and Kinesiology (J.W.), Texas A&M University, College Station, Texas 77843-4243; Washington University School of Medicine (I.B.B., D.C.R.), Division of Biostatistics, St. Louis, Missouri 61330; School of Nutrition and Public Health (G.R.C.), Deakin University, Geelong 3217, Victoria, Australia; School of Kinesiology and Leisure Studies (A.S.L.), Minnesota University, Minneapolis, Minnesota 55455; Department of Kinesiology (J.S.S.), Indiana University, Bloomington, Indiana 47405; and Pennington Biomedical Research Center (M.C., C.B.), Louisiana State University, Baton Rouge, Louisiana 70808

Address correspondence and requests for reprints to: Yvon C. Chagnon, Ph.D., Physical Activity Sciences Laboratory, Kinesiology, PEPS 0212, Laval University, Ste-Foy, Québec, Canada, G1K 7P4. E-mail: yvon.chagnon{at}kin.msp.ulaval.ca

Linkage and association studies between three exonic polymorphisms in the leptin receptor gene and body composition variables in the HERITAGE Family Study were undertaken. Polymorphisms K109R, Q223R, and K656N have been analyzed with body mass index (BMI), sum of height skinfolds (SF8), fat mass (FM), percent body fat (%FAT), fat free mass, and plasma leptin level. Single-point linkage analysis and covariance analysis across genotypes were performed, by race, on phenotypes adjusted for age and sex. Blacks (88 parents; 231 adult offspring) from 115 nuclear families (72–119 sibpairs) and Caucasians (192 parents; 330 adult offspring) from 99 nuclear families (319–364 sibpairs) were used for these analyses. In Caucasians, BMI and FM showed suggestive linkages with K109R (P = 0.02 and P = 0.05, respectively) and associations with Q223R (P = 0.005 and P = 0.03, respectively). In blacks, no statistically significant linkage or association was observed. In Caucasians, associations with Q223R were observed in parents, but not in offspring, for BMI, FM, and %FAT (0.04 P 0.0001). Males, not females, showed differences across genotypes for the same phenotypes plus SF8 and leptin (0.03 P 0.0002). Carriers of the R223 allele showed higher values than noncarriers for BMI (+4 U, P = 0.0001), SF8 (+30 mm, P = 0.01), FM (+7 kg, P = 0.0004), %FAT (+5%, P = 0.0002), and leptin (+4 ng/mL, P = 0.0006). These results indicate a significant effect of leptin receptor on adiposity in middle-aged Caucasian males.

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